COVID-19 and Intracerebral Hemorrhage

The relationship between coronavirus disease 2019 (COVID-19) and intracerebral hemorrhage remains unclear.

In Mexico patients that debuted with pulmonary symptoms accounted for 68.6% of the cases with an interval between the development of symptoms and the presentation of hemorrhagic stroke (HS) of 15.6 days. Parra-Romero et al. found that the use of anticoagulants during hospitalization, multifocal image pattern, and the elevation of D-dimer, Ferritin, and lactate dehydrogenase levels were significantly associated with the group of pulmonary presentation, whereas the presence of hypertension during hospitalization, and a lower hemoglobin level was associated with the group of neurologic symptoms.

Although hemorrhagic stroke (HS) associated with COVID-19 is a clinical entity with increasing evidence, it is necessary to establish that there are two forms of presentation with their own characteristics 1).

Melmed et al. performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population 2).

Motoie et al. reported a case of severe COVID-19 pneumonia complicated by multiple simultaneous intracerebral hemorrhages (MSICH). The patient died eight days after the episode of MSICH. No apparent coagulopathy was observed; however, extracorporeal membrane oxygenation and anticoagulation might have caused the occurrence of MSICH. Laboratory findings showed hypercoagulability, suggesting that thrombotic etiologies, such as sinus thrombosis or cerebral infarction, might also have caused MSICH. MSICH can occur as a fatal complication of COVID-19, and this should be considered when providing treatment 3).

Kvernland et al. observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19 4).

Bao et al. reported the clinical features of a COVID-19 patient whose first symptom was cerebral hemorrhage. More importantly, after the craniotomy, the patient had high fever and it was difficult to retreat. After cerebrospinal fluid testing, it was determined that an intracranial infection had occurred. After anti-infection and plasma infusion of the recovered person, the patient's symptoms gradually improved. This case suggests that COVID-19 may infringe on cerebral blood vessels and cause cerebral hemorrhage. Transfusion of plasma from rehabilitation patients is effective for critically ill patients 5).

Khattar et al. reported a 42-year old COVID-19 positive patient with a fatal intracerebral hemorrhage (ICH). The patient presented with fever and dyspnea, requiring intubation due to medical complications. After prolonged sedation and anticoagulation, the patient suddenly developed bilaterally fixed and dilated pupils, caused by a right-sided intracranial hemorrhage with uncal herniation. The course of this case illustrates the delicate balance between hypercoagulability and coagulation factor depletion; especially in the intubated and sedated patient, in whom regular neurological assessments are impeded. As we expand our understanding of the neurological ramifications of COVID-19, clinicians need to be increasingly aware of the precarious coagulation balance 6).

Parra-Romero G, Navarro-Olvera JL, Beltrán-Mendoza JQ, Ruiz-Sandoval JL, Mar-Álvarez A, Aguado-Carrillo G, Teyes-Calva N, Rodríguez-Morales J, Martínez-Luna AA, Hernández-Valencia AF, Carrillo-Ruiz JD. Primary spontaneous intracerebral hemorrhage in COVID-19 patients: differences among presentation patterns - A systematic review. Cir Cir. 2022;90(6):734-741. English. doi: 10.24875/CIRU.21000813. PMID: 36472834.
Melmed KR, Cao M, Dogra S, Zhang R, Yaghi S, Lewis A, Jain R, Bilaloglu S, Chen J, Czeisler BM, Raz E, Lord A, Berger JS, Frontera JA. Risk factors for intracerebral hemorrhage in patients with COVID-19. J Thromb Thrombolysis. 2021 May;51(4):953-960. doi: 10.1007/s11239-020-02288-0. Epub 2020 Sep 24. PMID: 32968850; PMCID: PMC7511245.
Motoie R, Akai M, Kitahara T, et al. Coronavirus Disease 2019 Complicated by Multiple Simultaneous Intracerebral Hemorrhages [published online ahead of print, 2020 Sep 5]. Intern Med. 2020;10.2169/internalmedicine.5697-20. doi:10.2169/internalmedicine.5697-20
Kvernland A, Kumar A, Yaghi S, et al. Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System [published online ahead of print, 2020 Aug 24]. Neurocrit Care. 2020;1-12. doi:10.1007/s12028-020-01077-0
Bao Y, Lin SY, Cheng ZH, et al. Clinical Features of COVID-19 in a Young Man with Massive Cerebral Hemorrhage-Case Report [published online ahead of print, 2020 May 23]. SN Compr Clin Med. 2020;1-7. doi:10.1007/s42399-020-00315-y
Khattar NK, Sharma M, McCallum AP, et al. Intracranial hemorrhage in a young COVID-19 patient. Interdiscip Neurosurg. 2020;22:100878. doi:10.1016/j.inat.2020.100878
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